This Program Project has a central theme-the role of lipids, particularly eicosanoids, as neurotransmitters, intracellular second messengers and modulators of synaptic plasticity. We have identified through previous work and preliminary studies both biochemical and electrophysiological evidence that supports a role for these lipids in neural signaling. In the process, we have identified new neural lipid metabolic pathways and metabolites, 8(R)-lipoxygenase and 8-KETE, identified "unusual" nicotine acetylcholine receptors with sequence similarity to prostaglandin receptors, and identified strong links between lipid metabolism and synaptic plasticity in models of LTP and LTD in the mammalian hippocampus and in components in eicosanoid biochemistry, neural physiology and molecular biology. These methods are combined to address three major efforts: 1) What is the role of lipid modulators in long-term synaptic plasticity? 2) What is the role of lipid metabolites in presynaptic facilitation by nicotine? 3) Are eicosanoids pheromones in mammals? These Units are composed of investigators from 5 independent laboratories and are supported by a Core Unit devoted to lipid biochemistry.